EP0826657A1 - Verbindungen zur Modulierung von Hormonrezeptoren, diese enthaltende Zusammensetzungen und ihre Verwendung in Therapie - Google Patents

Verbindungen zur Modulierung von Hormonrezeptoren, diese enthaltende Zusammensetzungen und ihre Verwendung in Therapie Download PDF

Info

Publication number
EP0826657A1
EP0826657A1 EP97401999A EP97401999A EP0826657A1 EP 0826657 A1 EP0826657 A1 EP 0826657A1 EP 97401999 A EP97401999 A EP 97401999A EP 97401999 A EP97401999 A EP 97401999A EP 0826657 A1 EP0826657 A1 EP 0826657A1
Authority
EP
European Patent Office
Prior art keywords
radical
disorders
acne
skin
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP97401999A
Other languages
English (en)
French (fr)
Other versions
EP0826657B1 (de
Inventor
Etienne Thoreau
Braham Shroot
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Galderma Research and Development SNC
Original Assignee
Centre International de Recherches Dermatologiques Galderma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Centre International de Recherches Dermatologiques Galderma filed Critical Centre International de Recherches Dermatologiques Galderma
Publication of EP0826657A1 publication Critical patent/EP0826657A1/de
Application granted granted Critical
Publication of EP0826657B1 publication Critical patent/EP0826657B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/734—Ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
    • C07C47/277—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/72—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Definitions

  • the present invention relates to new modulator compounds families of cellular hormonal receptors such as those described by Guiguère or Evans (Guiguère V., Endocrine Reviews, 15.1, 1994.61; Mangelsdorf D. & Evans R., Cell, 83, 1995, 841).
  • these new compounds exert biological activity on animal cells and tissues with regard to their differentiation, their proliferation or their implication in cell death (apoptosis).
  • These substances act in combination with known ligands from the super family, for example retinoic acid and retinoids, vitamin D3, thyroid hormone, estrogen, etc., so as to improve their risk / benefit ratio, both by reducing their toxicity and by improving their pharmacological efficacy.
  • the compounds according to the invention allow the prevention and / or the treatment of disorders and / or conditions linked to overregulation of receptors related to these hormones or vitamins. They may also be involved in the control of the different stages of the metabolism or catabolism of these hormones or vitamins.
  • salts these are preferably salts of an alkali or alkaline earth metal or still zinc or an organic amine.
  • lower alkyl radical means a radical having from 1 to 6 carbon atoms, linear or branched, preferably the methyl, ethyl, isopropyl, butyl, tert-butyl and hexyl radicals. This definition also applies to the alkyl residues of the alkoxy radicals.
  • cycloalkoxyl is preferably understood according to the invention the radicals the cycloalkyl radical of which consists of a mono group or polycyclic, comprising 3 to 12 carbon atoms, optionally substituted by one or more lower alkyl radicals.
  • heterocycle preferably means a piperidino radical, morpholino, pyrrolidino or pizzaino, optionally substituted in position 4 by a lower alkyl radical.
  • Y represents a cyano radical (-CN) or a -COR 3 radical, R 3 being defined above, n represents 2, 3 or 4 and o represents 1, 2 or 3.
  • Z represents a methylene radical (-CH 2 -)
  • Y represents a -thiol (-SH), trimethylammonium (-N + (CH 3 ) 3 ) or cyano radical (-CN).
  • These compounds of formula (I) can be obtained in particular by reacting a hydroxylated compound of formula (II) in which X and R 2 are defined above, with a radical of formula (III) X- (CH 2 ) n -Z- (CH 2 ) o -Y in which Z, Y, n and o are defined above, and X represents a leaving group, such as a halogen, in particular bromine or iodine.
  • the hydroxylated compound of formula (II) is prepared from the derivative corresponding alkoxylated described in patent application DE 28 19 213, in particular the methoxylated derivative described in example 9.
  • the hydrolysis of the function ether is produced according to the usual methods of the technique, with protection and appropriate deprotection of functions sensitive to hydrolysis conditions.
  • R 2 represents the radical -COOH
  • the compounds are prepared by protecting R 2 with a protective group of alkyl, allylic, benzyl or tert-butyl type.
  • the phenol of formula is transformed general (II) into a compound of formula (I) with the radical of formula (III) in presence of potassium carbonate (K2CO3) in methyl ether ketone (MEK) or in the presence of sodium hydride in a solvent such as dimethylformamide (DMF).
  • K2CO3 potassium carbonate
  • MEK methyl ether ketone
  • DMF dimethylformamide
  • W represents an atom halogen such as bromine or iodine
  • ⁇ represents a protective group, such as terbutyldimethylsilane (TBDMSi)
  • R the radical - (CH2) n-Z- (CH2) o- and Y is such than in the request.
  • Reactions 1 / of Mitsunobu and 2 / of saponification are possibly performed if Y represents an oxygen atom and we want the transform into sulfur or nitrogen atom.
  • the examples below illustrate this reaction scheme.
  • the present invention also relates to the use of the compounds according to the invention as medicament and cosmetic compositions or pharmaceuticals comprising at least one compound of general formula (I) such as defined above and at least one vehicle cosmetically or pharmaceutically acceptable.
  • Cosmetic or pharmaceutical compositions containing at least one compound of formula (I) are in particular intended for the treatment of disorders or conditions linked to overregulation of transcription factors called retinoid receptors which include RARs (Retinoic Acid Receptors), including including the subtypes ⁇ , ⁇ , ⁇ , the Retinoic Receptors X (RXRs), including the subtypes ⁇ , ⁇ , ⁇ , or the genes comprising the response elements RARs and RXRs.
  • RARs Retinoic Acid Receptors
  • RXRs Retinoic Receptors X
  • overregulation of the RARs and / or RXRs receptors it is understood according to the invention an overexpression of the RARs and / or RXRs receptors, and / or a biological overactivity of RARs and / or RXRs receptors.
  • the biological overactivity of the RARs and / or RXRs receptors can be due to a chemical modification of the RARs and / or RXRs receptors, but it can may also be due to a factor other than the receiver itself. So the biological overactivity may be due to overexpression of an endogenous gene or to expression of an exogenous gene comprising the RARE response element (retinoic acid response element) on which a heterodimer including the RAR receptor, the latter carrying an agonist ligand.
  • RARE response element retinoic acid response element
  • an endogenous gene comprising the RARE response element we may include the CRABP II gene (cellular retinoic acid binding protein II), the overexpression has been demonstrated in psoriasis ("Overexpression of CRABP Il and down-regulation of CRABP I in psoriatic skin ", G. Siegenthaler et al., Dermatology 1992; 185: 251-256).
  • gene expression exogenous comprising the RARE response element we can cite the HIV-1 genome (human immunodeficiency virus) (Proc. Natl. Acad. Sci. USA, Lee et al., Vol. 91, pp.
  • the compounds of formula (I) can be advantageously used in combination with other compounds with activity of retinoid type, with vitamins D or their derivatives, with corticosteroids, with anti-free radicals , ⁇ -hydroxy or ⁇ -keto acids or their derivatives, or alternatively with ion channel blockers.
  • vitamins D or their derivatives is meant, for example, the derivatives of vitamin D 2 or D 3 and in particular 1,25-dihydroxyvitamin D 3 .
  • anti-free radicals is meant, for example, ⁇ -tocopherol, Super Oxide Dismutase, Ubiquinone or certain metal chelators.
  • ⁇ -hydroxy or ⁇ -keto acids or their derivatives is meant for example lactic, malic, citric, glycolic, mandelic, tartaric, glyceric or ascorbic acids or their salts, amides or esters.
  • ion channel blockers is meant, for example, Minoxidil (2,4-diamino-6-piperidino-pyrimidine-3-oxide) and its derivatives.
  • Cosmetic or pharmaceutical compositions comprising a effective amount of at least one compound of formula (I), one of its analogs chiral or one of its salts comprises a cosmetically or pharmaceutically acceptable and compatible with the mode of administration restrained.
  • the effective amount depends of course on the desired treatment and the nature of the compound chosen is therefore determined by a person skilled in the art.
  • the administration of the compounds according to the invention can be carried out by enteral, parenteral, topical or ocular.
  • the composition can be in the form of tablets, capsules, dragees, syrups, suspensions, solutions, powders, granules, emulsions, microspheres or nanospheres or lipid vesicles or polymers allowing controlled release.
  • the composition, more particularly the pharmaceutical composition can be present in the form of solutions or suspensions for infusion or for injection.
  • the compounds according to the invention are generally administered to a daily dose of approximately 0.01 mg / kg to 100 mg / kg in body weight, and this at reason for 1 to 3 takes.
  • the composition is more particularly intended for treatment of the skin and mucous membranes and can then be in the form ointments, creams, milks, ointments, powders, soaked tampons, solutions, gels, sprays, lotions, suspensions or shampoos. It can also be in the form of microspheres or nanospheres or lipid or polymer vesicles or polymer patches and hydrogels allowing controlled release.
  • This topical composition can by elsewhere be present either in anhydrous form or in an aqueous form.
  • composition for topical or ocular use contains at least one compound of formula (I) as defined above, or one of its analogs chirals or one of its salts, preferably at a concentration between 0.001% and 5% by weight relative to the total weight of the composition.
  • composition according to the invention may also contain additives inert or even pharmacodynamically or cosmetically active or combinations of these additives, and in particular: wetting agents; agents depigmenters such as hydroquinone, azelaic acid, caffeic acid or kojic acid; emollients; moisturizers such as glycerol, PEG 400, thiamorpholinone, and its derivatives or even urea; agents antiseborrhoeic or anti-acne, such as S-carboxymethylcysteine, S-benzyl-cysteamine, their salts or derivatives, or benzoyl peroxide; of antibiotics like erythromycin and its esters, neomycin, clindamycin and its esters, tetracyclines; antifungal agents such as ketoconazole or polymethylene-4,5 isothiazolidones-3; agents promoting regrowth hair, such as Minoxidil (2,4-diamino-6-piperidin
  • composition may also contain agents for improving flavor, preservatives such as acid esters parahydroxybenzoic, stabilizing agents, regulating agents humidity, pH regulating agents, pressure modifying agents osmotic, emulsifying agents, UV-A and UV-B filters, antioxidants, such as ⁇ -tocopherol, butylhydroxyanisole or butylhydroxytoluene.
  • preservatives such as acid esters parahydroxybenzoic, stabilizing agents, regulating agents humidity, pH regulating agents, pressure modifying agents osmotic, emulsifying agents, UV-A and UV-B filters, antioxidants, such as ⁇ -tocopherol, butylhydroxyanisole or butylhydroxytoluene.
  • tert-butyldimethylsilyl chloride (2.64 g) is added to a mixture of 5- (3-bromo-5,5,8 , 8-tetramethyl-5,6,7,8-tetrahydro-naphthalene-2-yloxy) -pentan-1-ol (4.3g, 11.7 mmol) and 80% sodium hydride (422 mg) in THF (20ml). The mixture is stirred at room temperature for 2 h. The solution is poured into a mixture of water and ethyl acetate.
  • the organic phase is washed twice with water, dried over magnesium sulfate, and concentrated on a rotary evaporator under vacuum at 40 ° C.
  • the product is purified by flash chromatography on a silica column. Yellow oil. Yield: 64%.
  • the filtrate is poured into an ethyl ether / water mixture.
  • the organic phase is washed with water, dried over anhydrous magnesium sulfate, concentrated on a rotary evaporator under vacuum at 40 ° C.
  • the resulting oil is dissolved in 30 ml of dichloromethane and 2 g of pyridinium dichromate (PDC) are added.
  • PDC pyridinium dichromate
  • the mixture is stirred for 4 hours at room temperature, filtered through silica.
  • the filtrate is concentrated on a rotary evaporator under vacuum at 40 ° C and purified by flash chromatography on a silica column. Colorless oil. Yield: 61%.
  • the mixture is acidified to pH 1 with a solution of concentrated hydrochloric acid. After decantation, the organic phase is washed twice with water, dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator under vacuum at 40 ° C. Colorless oil. Yield: 100%.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Nutrition Science (AREA)
  • Diabetes (AREA)
  • Biotechnology (AREA)
  • Obesity (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Furan Compounds (AREA)
  • Pyrane Compounds (AREA)
EP97401999A 1996-09-02 1997-08-27 Verbindungen zur Modulierung von Hormonrezeptoren, diese enthaltende Zusammensetzungen und ihre Verwendung in Therapie Expired - Lifetime EP0826657B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR9610686A FR2752837B1 (fr) 1996-09-02 1996-09-02 Nouveaux composes modulateurs des recepteurs hormonaux, les compositions les comprenant et leur utilisation en therapie
FR9610686 1996-09-02

Publications (2)

Publication Number Publication Date
EP0826657A1 true EP0826657A1 (de) 1998-03-04
EP0826657B1 EP0826657B1 (de) 2001-08-01

Family

ID=9495359

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97401999A Expired - Lifetime EP0826657B1 (de) 1996-09-02 1997-08-27 Verbindungen zur Modulierung von Hormonrezeptoren, diese enthaltende Zusammensetzungen und ihre Verwendung in Therapie

Country Status (12)

Country Link
US (1) US5910508A (de)
EP (1) EP0826657B1 (de)
JP (1) JP2910995B2 (de)
AT (1) ATE203743T1 (de)
AU (1) AU703076B2 (de)
CA (1) CA2213609C (de)
DE (1) DE69705902T2 (de)
DK (1) DK0826657T3 (de)
ES (1) ES2163723T3 (de)
FR (1) FR2752837B1 (de)
GR (1) GR3036997T3 (de)
PT (1) PT826657E (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009156675A2 (fr) 2008-05-30 2009-12-30 Galderma Research & Development Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé et un rétinoïde
EP2460562A1 (de) 2006-12-21 2012-06-06 Galderma Research & Development Creme-Gel mit mindestens einem Retinoid und Benzoylperoxid
EP2460561A1 (de) 2006-12-21 2012-06-06 Galderma Research & Development Emulsion mit mindestens einem Retinoid und Benzoylperoxid

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7655699B1 (en) 1992-04-22 2010-02-02 Eisai Inc. Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors
TR200200507T2 (tr) 1999-08-27 2002-10-21 Ligand Pharmaceuticals Inc Androjen reseptörü modülatör bileşikleri ve metotları
US6566372B1 (en) 1999-08-27 2003-05-20 Ligand Pharmaceuticals Incorporated Bicyclic androgen and progesterone receptor modulator compounds and methods
WO2001016133A2 (en) 1999-08-27 2001-03-08 Ligand Pharmaceuticals Incorporated 8-substituted-6-trifluoromethyl-9-pyrido[3,2-g]quinoline compounds as androgen receptor modulators
WO2001019770A2 (en) * 1999-09-14 2001-03-22 Ligand Pharmaceuticals Incorporated Rxr modulators with improved pharmacologic profile
US8026280B2 (en) 2001-03-27 2011-09-27 Errant Gene Therapeutics, Llc Histone deacetylase inhibitors
US7312247B2 (en) * 2001-03-27 2007-12-25 Errant Gene Therapeutics, Llc Histone deacetylase inhibitors
US7842727B2 (en) * 2001-03-27 2010-11-30 Errant Gene Therapeutics, Llc Histone deacetylase inhibitors
US6495719B2 (en) 2001-03-27 2002-12-17 Circagen Pharmaceutical Histone deacetylase inhibitors
CA2486303C (en) * 2002-05-22 2013-04-30 Errant Gene Therapeutics, Llc Histone deacetylase inhibitors based on alpha-ketoepoxide compounds
CA2506504A1 (en) * 2002-11-20 2004-06-03 Errant Gene Therapeutics, Llc Treatment of lung cells with histone deacetylase inhibitors
WO2006052916A2 (en) * 2004-11-08 2006-05-18 Errant Gene Therapeutics, Inc. Histone deacetylase inhibitors
EP2742350B1 (de) 2011-08-08 2019-10-30 The Coca-Cola Company Zelllinien mit endogenen geschmacksrezptoren und deren verwendungen
KR102170307B1 (ko) * 2012-11-15 2020-10-26 주식회사 알엔에스 탈모방지 및 모발성장 촉진제 조성물
JP2021503464A (ja) * 2017-11-17 2021-02-12 アイオー セラピューティクス インコーポレイテッド レチノイドｘ受容体特異的なレチノイドの調製のための化合物および合成方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2390428A1 (fr) * 1977-05-04 1978-12-08 Hoffmann La Roche Nouveaux composes polyeniques, leur preparation et leur application en tant que medicaments
EP0568898A1 (de) * 1992-05-07 1993-11-10 F. Hoffmann-La Roche Ag Benzothiepin-, Benzothiopyran- und Benzothiophenderivate, deren Herstellung und Verwendung als Heilmittel
WO1995004036A1 (en) * 1993-01-11 1995-02-09 Ligand Pharmaceuticals Inc. Compounds having selective activity for retinoid x receptors, and means for modulation of processes mediated by retinoid x receptors

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU626881B2 (en) * 1988-07-14 1992-08-13 F. Hoffmann-La Roche Ag Benzofused heterocyclics used as pharmaceuticals
EP0983992B1 (de) * 1992-04-22 2005-10-26 Ligand Pharmaceuticals Incorporated Verbindungen mit Retinoid x rezeptorselektivität

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2390428A1 (fr) * 1977-05-04 1978-12-08 Hoffmann La Roche Nouveaux composes polyeniques, leur preparation et leur application en tant que medicaments
EP0568898A1 (de) * 1992-05-07 1993-11-10 F. Hoffmann-La Roche Ag Benzothiepin-, Benzothiopyran- und Benzothiophenderivate, deren Herstellung und Verwendung als Heilmittel
WO1995004036A1 (en) * 1993-01-11 1995-02-09 Ligand Pharmaceuticals Inc. Compounds having selective activity for retinoid x receptors, and means for modulation of processes mediated by retinoid x receptors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KOCH S S C ET AL: "Identification of the First Retinoid X Receptor Homodimer Antagonist", J. MED. CHEM. (JMCMAR,00222623);96; VOL.39 (17); PP.3229-3234, LIGAND PHARMACEUTICALS INC.;DEPARTMENT OF RETINOID CHEMISTRY RESEARCH; SAN DIEGO; 92121; CA; USA (US), XP002030143 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2460562A1 (de) 2006-12-21 2012-06-06 Galderma Research & Development Creme-Gel mit mindestens einem Retinoid und Benzoylperoxid
EP2460561A1 (de) 2006-12-21 2012-06-06 Galderma Research & Development Emulsion mit mindestens einem Retinoid und Benzoylperoxid
EP3025763A1 (de) 2006-12-21 2016-06-01 Galderma Research & Development Cremegel, das mindestens ein retinoid und benzoylperoxid umfasst
WO2009156675A2 (fr) 2008-05-30 2009-12-30 Galderma Research & Development Nouvelles compositions dépigmentantes sous forme d'une composition anhydre sans vaseline et sans élastomère comprenant un dérivé phénolique solubilisé et un rétinoïde

Also Published As

Publication number Publication date
ATE203743T1 (de) 2001-08-15
JPH10101641A (ja) 1998-04-21
AU3605997A (en) 1998-03-05
US5910508A (en) 1999-06-08
FR2752837B1 (fr) 1999-11-12
CA2213609A1 (fr) 1998-03-02
GR3036997T3 (en) 2002-01-31
JP2910995B2 (ja) 1999-06-23
DE69705902T2 (de) 2001-11-15
ES2163723T3 (es) 2002-02-01
CA2213609C (fr) 2002-06-25
DK0826657T3 (da) 2001-10-22
FR2752837A1 (fr) 1998-03-06
AU703076B2 (en) 1999-03-11
PT826657E (pt) 2001-12-28
EP0826657B1 (de) 2001-08-01
DE69705902D1 (de) 2001-09-06

Similar Documents

Publication Publication Date Title
EP0826657B1 (de) Verbindungen zur Modulierung von Hormonrezeptoren, diese enthaltende Zusammensetzungen und ihre Verwendung in Therapie
CA2224528C (fr) Composes stilbeniques a groupement adamantyl, compositions les contenant et utilisations
CA2147806C (fr) Composes polyeniques, compositions pharmaceutiques et cosmetiques les contenant et utilisations
FR2733684A1 (fr) Utilisation de retinoides dans une composition cosmetique ou pour la fabrication d'une composition pharmaceutique
FR2763588A1 (fr) Composes triaromatiques, compositions les contenant et utilisations
EP0915823B1 (de) Bisaromatische verbindungen, sie enthaltende pharmazeutische und kosmetische zusammensetzungen und verwendungen
CA2191790C (fr) Composes biaromatiques portant un groupement adamantyl en para, compositions pharmaceutiques et cosmetiques les contenant et utilisations de ces compositions
EP0832081A1 (de) Bicyclische aromatische verbindungen
EP0832057B1 (de) Diaromatische propynyl- oder dienylverbindungen
FR2776657A1 (fr) Composes bicycliques-aromatiques et leur utilisation en medecine humaine ou veterinaire ainsi qu'en cosmetologie
EP0977749B1 (de) Bi-aromatische verbindungen und diese enthaltende pharmazeutische und kosmetische zusammenstellungen
LU86345A1 (fr) Nouveaux derives benzofuranniques,leurs procedes de preparation et compositions medicamenteuse et cosmetique les contenant
EP0816352A1 (de) Biaryl heterocyclische Verbindungen und ihre Verwendung in der Human- oder Tiermedizin und in der Kosmetik
EP1086080B1 (de) Diarylselenid-verbindungen und ihre verwendung in menschliche oder tierische medizin wie in kosmetologie
EP0986537B1 (de) Hetero-ethynyl-verbindungen und diese enthaltende zusammensetzungen und kosmetika
WO1998024778A1 (fr) Derives d'acides benzofuranne-acryliques et leur utilisation comme modulateurs des recepteurs rxrs ou rars
EP0934295B1 (de) Bioaromatische dibenzofuranderivate und verwendung in der human- oder tiermedizin und in der kosmetik
EP0952975A1 (de) Eine heteroethynylen-brücke enthaltende bi-aromatische verbindungen und diese enthaltende pharmazeutische und kosmetische zusammensetzungen

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;RO;SI

DAX Request for extension of the european patent (deleted)
17P Request for examination filed

Effective date: 19980131

AKX Designation fees paid

Free format text: AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

RBV Designated contracting states (corrected)

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 19990510

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

REF Corresponds to:

Ref document number: 203743

Country of ref document: AT

Date of ref document: 20010815

Kind code of ref document: T

ITF It: translation for a ep patent filed
REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20010827

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: FRENCH

REF Corresponds to:

Ref document number: 69705902

Country of ref document: DE

Date of ref document: 20010906

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

GBT Gb: translation of ep patent filed (gb section 77(6)(a)/1977)

Effective date: 20011101

REG Reference to a national code

Ref country code: PT

Ref legal event code: SC4A

Free format text: AVAILABILITY OF NATIONAL TRANSLATION

Effective date: 20011008

REG Reference to a national code

Ref country code: GB

Ref legal event code: IF02

REG Reference to a national code

Ref country code: GR

Ref legal event code: EP

Ref document number: 20010401870

Country of ref document: GR

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2163723

Country of ref document: ES

Kind code of ref document: T3

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20020301

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20040803

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20040806

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20040810

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IE

Payment date: 20040811

Year of fee payment: 8

Ref country code: AT

Payment date: 20040811

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FI

Payment date: 20040812

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DK

Payment date: 20040813

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20040825

Year of fee payment: 8

Ref country code: ES

Payment date: 20040825

Year of fee payment: 8

Ref country code: PT

Payment date: 20040825

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 20040827

Year of fee payment: 8

Ref country code: CH

Payment date: 20040827

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20040902

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20041021

Year of fee payment: 8

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES;WARNING: LAPSES OF ITALIAN PATENTS WITH EFFECTIVE DATE BEFORE 2007 MAY HAVE OCCURRED AT ANY TIME BEFORE 2007. THE CORRECT EFFECTIVE DATE MAY BE DIFFERENT FROM THE ONE RECORDED.

Effective date: 20050827

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050827

Ref country code: FI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050827

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050827

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050828

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050829

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050829

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050831

Ref country code: DK

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050831

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050831

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20050831

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20060227

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20060301

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20060301

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20060302

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: DK

Ref legal event code: EBP

EUG Se: european patent has lapsed
GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20050827

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20060428

NLV4 Nl: lapsed or anulled due to non-payment of the annual fee

Effective date: 20060301

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20060428

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20050829

BERE Be: lapsed

Owner name: CENTRE INTERNATIONAL DE RECHERCHES DERMATOLOGIQUES

Effective date: 20050831